The concentration of potassium in the brain's extracellular fluid ([K]ECF) is tightly regulated despite acute or chronic changes in the plasma potassium concentration. However, we have observed in three different animal models of hypertension that [K]ECF in brain is significantly reduced compared to normotensive control animals. Furthermore, chronic infusions of small amounts of potassium into the cerebral ventricles of DOCA-salt rats prevents the development of hypertension. Consequently, we hypothesize that the regulatory systems that are involved in controlling [K]ECF in brain also control blood pressure. This project is designed to provide further support for this hypothesis and to examine the roles of two regulatory systems that may control both brain [K]ECF and blood pressure. The specific aims are to: 1) determine the relationship between blood pressure and [K]ECF of brain in normotensive and hypertensive animals and during central or dietary potassium supplementation. 2) identify the abnormality in brain potassium homeostasis which accounts for the decreased [K]ECF in hypertensive animals. 3) determine the roles of the sympathetic nervous system and brain ouabain-like factor in regulation of brain [K]ECF. Many previous clinical and animal studies have suggested an inverse relation between dietary potassium intake and blood pressure. Our studies could define the physiological basis for this relationship while, at the same time, providing new information on how [K]ECF is regulated. The demonstration that [K]ECF is the important potassium-related variable in hypertension could ultimately lead to new therapeutic approaches.